Association of Serum Klotho with Loss of Bone Mineral Density and Fracture Risk in Older Adults

Objectives: Klotho deficiency has been previously linked to aging-like phenotypes such as osteoporosis, cognitive impairment, and sarcopenia. Low serum klotho was shown to be related to grip strength and disability. Nonetheless, no previous study has explored the association between serum klotho and fractures. The purpose of this report is to examine the relationship of serum klotho with bone mineral density (BMD) loss and fractures in older adults. Design: The Health, Aging, and Body Composition (Health ABC) Study is a longitudinal cohort study of 3,075 community-dwelling older adults. Setting: US clinical centers. Participants: Two thousand seven hundred and seventy six well-functioning black and white adults aged 70 to 79 years with serum klotho measurements were followed up for a median of 5 years. Measurements: Percent annualized BMD change and fracture risk were compared across klotho quartiles. A Poisson distribution was used to calculate age-adjusted fracture incidence rates, and Cox proportional hazards models for multivariable-adjusted hazard ratios. Results: The annualized percent changes in hip, femoral neck, and vertebral BMD were similar across klotho quartiles. Participants experienced 507 nonspine fractures, 203 hip fractures, and 135 vertebral fractures. The Incidence rate (IR) of nonspine fractures was 17 per 1,000 person-years. The most frequent site was hip (IR = 6 per 1,000 person-years) and the IR of vertebral fractures was 3 per 1,000 person-years. There was no association between the lowest quartile of plasma klotho and nonspine (hazard ratio (HR) = 1.19, 95% confidence interval (CI) = 0.86–1.65), hip (HR = 1.34, 95% CI = 0.79–2.27), or vertebral fractures (HR = 1.17, 95% CI = 0.65–2.11). Conclusion: Although klotho gene is a susceptible gene for reduced BMD, klotho blood concentration does not appear to be a predictor of bone loss or fracture risk in well-functioning older adults.